Interferon-alpha reduces catecholamine secretion from bovine adrenal chromaffin cells stimulated by acetylcholine.
A long-term pretreatment (72 h) of bovine adrenal chromaffin cells with recombinant human interferon (IFN) -alpha-2b (1500 units/ml) produced a decrease in the secretion of catecholamines from the cells stimulated by acetylcholine (ACh) (25 micromol/l) but not that with human fibloblast IFN-beta (3000 units/ml) or recombinant human IFN-gamma (3000 units/ml). IFN-alpha-2b inhibited the ACh-induced secretion in a concentration- (30-1500 units/ml) and time-dependent manner (18-72 h). The content of catecholamines in the cells treated with IFN-alpha-2b for 72 h did not change. The inhibitory effect of IFN-alpha-2b on the secretion was abolished when the cells were simultaneously treated with anti-IFN-alpha antibody, and it was overcome by the increase in the external ACh concentration. IFN-alpha-2b also inhibited ACh-induced Ca2+ influx into the cells in a concentration-dependent manner similar to that of the IFN-alpha-2b inhibiting ACh-induced secretion. On the other hand, IFN-alpha-2b failed to reduce the secretion from the cells induced by high K+. These results strongly suggest that IFN-alpha-2b reduces the ACh-induced secretion of catecholamines from bovine adrenal chromaffin cells due to modulating the gene expression of the nicotinic ACh receptor-operated cation channels rather than due to directly affecting the channels. The results further indicate that the IFN-alpha-2b inhibition may be associated with the psychiatric side effects of IFN-alpha (depression, neurasthenica and somnolence, etc.), and that immune systems may regulate the function of (autonomic) nervous systems or adrenal medulla via IFN-alpha in vivo.
Tachikawa
E
E
Department of Pharmacology, School of Medicine, Iwate Medical University, Morioka, Japan.
Kondo
Y
Y
Takahashi
M
M
Kashimoto
T
T
Yanagihara
N
N
Toyohira
Y
Y
Izumi
F
F
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002395:Catecholamines / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D019439:Chromaffin Cells / Q000187:drug effects* / Q000378:metabolism; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000494:pharmacology*; D007372:Interferons / Q000494:pharmacology; D011994:Recombinant Proteins
D002395:Catecholamines; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D007372:Interferons; D000109:Acetylcholine; D002118:Calcium